Brain Death and Cold Storage Induce Renal Inflammation and Injury in an Experimental Model

Brain death (BD) and cold storage (CS) are key determinants of donor kidney quality and transplant outcomes. Although both processes are known to induce inflammation, the temporal hierarchy and molecular specificity of inflammatory activation during organ preservation remain poorly defined. This study investigated the inflammatory and histopathological evolution of donor kidneys following BD and during CS using an experimental rat model.

Rats were assigned to sham, BD, or BD followed by 12 or 24 hours of CS. In BD animals, contralateral kidneys were stored for different durations, allowing paired analysis across preservation times. Hemodynamic parameters, serum creatinine, inflammatory gene expression, and histopathological injury were evaluated.

BD induced hemodynamic instability and early renal dysfunction, reflected by increased serum creatinine levels and upregulation of inflammatory mediators. During CS, expression of Toll-like receptor 4, CASP1, interleukin-1β, and tumor necrosis factor-α remained elevated, while interleukin-6 increased progressively, particularly between BD and 12 hours of CS. In contrast, NLRP3 expression did not significantly increase during preservation. Histopathological analysis demonstrated progressive renal injury with increasing CS duration, including tubular and glomerular damage and features of acute tubular necrosis.

BD-induced inflammation persists throughout CS, supporting the concept that organ preservation represents an active injury phase rather than a passive metabolic pause. Distinct temporal inflammatory signatures during preservation highlight molecular pathways that may be targeted to mitigate preservation-associated injury.